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Re: TCA-Thorazine resemblances, and more zeugma

Posted by Sad Panda on May 29, 2004, at 0:31:22

In reply to TCA-Thorazine resemblances, and more Sad Panda, posted by zeugma on May 27, 2004, at 20:17:25

> > >
> > > >
> > > > What does your book tell you about the receptor blocking affinities of clomipramine? Probably both 5HT-1A and 5HT 2A blockade is therapeutic for me. The great experiment will be to see what 5HT reuptake inhibition does for me, since I have never taken one long enough to determine the nature of its effects. My hope is that the other actions of clomipramine will make the SRI effects tolerable.
> > > > >
> > > >
> > > >
> > >
> > > Clomipramine
> > >
> > > NE reuptake............+++
> > > 5HT reuptake........+++++
> > > DA reuptake..............+
> > > Blockade 5HT1.........+
> > > Blockade 5HT2.......+++
> > > Blockade ACh.........+++
> > > Blockade H1...........+++
> > > Blockade alpha-1....+++
> > > Blockade alpha-2......+
> > > Blockade D2............++
> > >
> > > where each + represents a difference of one order of magnitude for Ki, ranging from
> > >
> > > +++++ represents Ki = 0.1-1.0
> > > + represents Ki = 1000-10000
> > >
> > >
> > > Todd
> > >
> >
> > Hi Todd,
> >
> > If one + equals a range of 1000-10000, then I would say that + and ++ are would be clinically insignificant. Do you think you could put up some data for the other TCA's? I am fascinated that clomipramine gets a ++ for D2 blockade & I'd also like to see the comparison of the different TCA's that this book offers.
> >
> > Cheers,
> > Panda.
>
> Clomipramine's ++ for D2 blockade is actually unsurprising, given its remarkable structural resemblance to chlorpromazine {Thorazine}; clomipramine actually resembles a cross between imipramine and chlorpromazine, and early investigators seem to have fully expected this drug to be an antipsychotic (of course, all of the tertiary amine TCA's were first tested as AP's, as they all appear on paper to be minor variations on the Thorazine theme).
>
> As to TCA + stimulant simulating an MAOI, while this may crudely be true, on reflection I am more doubtful. I wonder if any who have been on this combination can report on its effects. I also think (simply going on my experiences with nortriptyline and atomoxetine, and KV's contrasting impressions of desipramine and nortriptyline) that the three major tertiary amine TCA's have significant differences between them, and that Effexor would be in a class of its own.
>
>
> >
> >
>
>

The differences between desipramine & nortriptyline are similar to the differences between imipramine & amitriptyline. Imipiramine is a weak H1 & 5-HT2A blocker while amitriptyline is potent. Amitriptyline is also a milder SRI than imipramine & clomipramine & can be cautiously combined with MAOI's, although I can't imagine a benefit to this. I would think doxepin or nortriptyline would be the ideal TCA's for useage with MAOI's as both are 5-HT2A bloackers & NRI's with no real SRI activity.

Cheers,
Panda.


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poster:Sad Panda thread:348690
URL: http://www.dr-bob.org/babble/20040527/msgs/351737.html